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ALDH1-high ovarian cancer stem-like cells can be isolated from serous and clear cell adenocarcinoma cells, and ALDH1 high expression is associated with poor prognosis.

Kuroda T, Hirohashi Y, Torigoe T, Yasuda K, Takahashi A, Asanuma H, Morita R, Mariya T, Asano T, Mizuuchi M, Saito T, Sato N - PLoS ONE (2013)

Bottom Line: ALDH1(high) cells could also be isolated from 8 of 11 primary ovarian carcinoma samples.Immunohistochemical staining revealed that higher ALDH1 expression levels in ovary cancer cases are related to poorer prognosis in both serous adenocarcinoma cases and clear cell adenocarcinoma cases.Taken together, the results indicate that ALDH1 is a marker for ovarian CSCs/CICs and that the expression level of ALDH1 might be a novel biomarker for prediction of poor prognosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Chuo-Ku, Sapporo, Japan.

ABSTRACT
Cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) are defined as a small population of cancer cells that have high tumorigenicity. Furthermore, CSCs/CICs are resistant to several cancer therapies, and CSCs/CICs are therefore thought to be responsible for cancer recurrence after treatment and distant metastasis. In epithelial ovarian cancer (EOC) cases, disease recurrence after chemotherapy is frequently observed, suggesting ovarian CSCs/CICs are involved. There are four major histological subtypes in EOC, and serous adenocarcinoma and clear cell adenocarcinoma are high-grade malignancies. We therefore analyzed ovarian CSCs/CICs from ovarian carcinoma cell lines (serous adenocarcinoma and clear cell adenocarcinoma) and primary ovarian cancer cells in this study. We isolated ovarian CSCs/CICs as an aldehyde dehydrogenase 1 high (ALDH1(high)) population from 6 EOC cell lines (3 serous adenocarcinomas and 3 clear cell adenocarcinomas) by the ALDEFLUOR assay. ALDH1(high) cells showed greater sphere-forming ability, higher tumorigenicity and greater invasive capability, indicating that ovarian CSCs/CICs are enriched in ALDH1(high) cells. ALDH1(high) cells could also be isolated from 8 of 11 primary ovarian carcinoma samples. Immunohistochemical staining revealed that higher ALDH1 expression levels in ovary cancer cases are related to poorer prognosis in both serous adenocarcinoma cases and clear cell adenocarcinoma cases. Taken together, the results indicate that ALDH1 is a marker for ovarian CSCs/CICs and that the expression level of ALDH1 might be a novel biomarker for prediction of poor prognosis.

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ALDEFLUOR assay for 6 epithelial ovarian cancer cell lines.ALDH1high cells were detected in 3 serous adenocarcinoma cell lines (AMOC-2, HUOA and OVCAR-3) and in 3 clear cell adenocarcinoma cell lines (ES-2, RMG-1 and TOV-21G). SSC-A: single strand conformation analysis. BAAA: boron-dipyrromethene- aminoacetaldehyde. FITC-A: fluorescein isothiocyanate analysis. Percentages in boxes indicate ALDH1high cell ratios. Diethylaminobenzaldehyde (DEAB), an ALDH-specific inhibitor, was used as a negative control.
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pone-0065158-g001: ALDEFLUOR assay for 6 epithelial ovarian cancer cell lines.ALDH1high cells were detected in 3 serous adenocarcinoma cell lines (AMOC-2, HUOA and OVCAR-3) and in 3 clear cell adenocarcinoma cell lines (ES-2, RMG-1 and TOV-21G). SSC-A: single strand conformation analysis. BAAA: boron-dipyrromethene- aminoacetaldehyde. FITC-A: fluorescein isothiocyanate analysis. Percentages in boxes indicate ALDH1high cell ratios. Diethylaminobenzaldehyde (DEAB), an ALDH-specific inhibitor, was used as a negative control.

Mentions: Several methods to isolate CSCs/CICs have already been described [12], and an aldehyde dehydrogenase 1 high population (ALDH1high) identified by the ALDEFLUOR assay was described to be enriched with CSCs/CICs. [20] We therefore analyzed ovarian carcinoma cell lines by the ALDEFLUOR assay to isolate ovarian CSCs/CICs. We investigated 3 human ovarian serous adenocarcinoma cell lines (AMOC-2, HUOA and OVCAR-3) and 3 human clear cell adenocarcinoma cell lines (ES-2, RMG-1 and TOV-21G) (Figure 1). ALDH1high population was identified in all ovarian carcinoma line cells, and the ratio of ALDH1high cells ranged from 0.7% for ES-2 cells to 7.9% for TOV-21G cells. We could isolate ALDH1high cells stably from 4 cell lines (AMOC-2, ES-2, RMG-1 and TOV-21G), and we therefore used these cell lines for further analysis.


ALDH1-high ovarian cancer stem-like cells can be isolated from serous and clear cell adenocarcinoma cells, and ALDH1 high expression is associated with poor prognosis.

Kuroda T, Hirohashi Y, Torigoe T, Yasuda K, Takahashi A, Asanuma H, Morita R, Mariya T, Asano T, Mizuuchi M, Saito T, Sato N - PLoS ONE (2013)

ALDEFLUOR assay for 6 epithelial ovarian cancer cell lines.ALDH1high cells were detected in 3 serous adenocarcinoma cell lines (AMOC-2, HUOA and OVCAR-3) and in 3 clear cell adenocarcinoma cell lines (ES-2, RMG-1 and TOV-21G). SSC-A: single strand conformation analysis. BAAA: boron-dipyrromethene- aminoacetaldehyde. FITC-A: fluorescein isothiocyanate analysis. Percentages in boxes indicate ALDH1high cell ratios. Diethylaminobenzaldehyde (DEAB), an ALDH-specific inhibitor, was used as a negative control.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3675199&req=5

pone-0065158-g001: ALDEFLUOR assay for 6 epithelial ovarian cancer cell lines.ALDH1high cells were detected in 3 serous adenocarcinoma cell lines (AMOC-2, HUOA and OVCAR-3) and in 3 clear cell adenocarcinoma cell lines (ES-2, RMG-1 and TOV-21G). SSC-A: single strand conformation analysis. BAAA: boron-dipyrromethene- aminoacetaldehyde. FITC-A: fluorescein isothiocyanate analysis. Percentages in boxes indicate ALDH1high cell ratios. Diethylaminobenzaldehyde (DEAB), an ALDH-specific inhibitor, was used as a negative control.
Mentions: Several methods to isolate CSCs/CICs have already been described [12], and an aldehyde dehydrogenase 1 high population (ALDH1high) identified by the ALDEFLUOR assay was described to be enriched with CSCs/CICs. [20] We therefore analyzed ovarian carcinoma cell lines by the ALDEFLUOR assay to isolate ovarian CSCs/CICs. We investigated 3 human ovarian serous adenocarcinoma cell lines (AMOC-2, HUOA and OVCAR-3) and 3 human clear cell adenocarcinoma cell lines (ES-2, RMG-1 and TOV-21G) (Figure 1). ALDH1high population was identified in all ovarian carcinoma line cells, and the ratio of ALDH1high cells ranged from 0.7% for ES-2 cells to 7.9% for TOV-21G cells. We could isolate ALDH1high cells stably from 4 cell lines (AMOC-2, ES-2, RMG-1 and TOV-21G), and we therefore used these cell lines for further analysis.

Bottom Line: ALDH1(high) cells could also be isolated from 8 of 11 primary ovarian carcinoma samples.Immunohistochemical staining revealed that higher ALDH1 expression levels in ovary cancer cases are related to poorer prognosis in both serous adenocarcinoma cases and clear cell adenocarcinoma cases.Taken together, the results indicate that ALDH1 is a marker for ovarian CSCs/CICs and that the expression level of ALDH1 might be a novel biomarker for prediction of poor prognosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Chuo-Ku, Sapporo, Japan.

ABSTRACT
Cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) are defined as a small population of cancer cells that have high tumorigenicity. Furthermore, CSCs/CICs are resistant to several cancer therapies, and CSCs/CICs are therefore thought to be responsible for cancer recurrence after treatment and distant metastasis. In epithelial ovarian cancer (EOC) cases, disease recurrence after chemotherapy is frequently observed, suggesting ovarian CSCs/CICs are involved. There are four major histological subtypes in EOC, and serous adenocarcinoma and clear cell adenocarcinoma are high-grade malignancies. We therefore analyzed ovarian CSCs/CICs from ovarian carcinoma cell lines (serous adenocarcinoma and clear cell adenocarcinoma) and primary ovarian cancer cells in this study. We isolated ovarian CSCs/CICs as an aldehyde dehydrogenase 1 high (ALDH1(high)) population from 6 EOC cell lines (3 serous adenocarcinomas and 3 clear cell adenocarcinomas) by the ALDEFLUOR assay. ALDH1(high) cells showed greater sphere-forming ability, higher tumorigenicity and greater invasive capability, indicating that ovarian CSCs/CICs are enriched in ALDH1(high) cells. ALDH1(high) cells could also be isolated from 8 of 11 primary ovarian carcinoma samples. Immunohistochemical staining revealed that higher ALDH1 expression levels in ovary cancer cases are related to poorer prognosis in both serous adenocarcinoma cases and clear cell adenocarcinoma cases. Taken together, the results indicate that ALDH1 is a marker for ovarian CSCs/CICs and that the expression level of ALDH1 might be a novel biomarker for prediction of poor prognosis.

Show MeSH
Related in: MedlinePlus